title: Identification of the shortest Aβ-peptide generating highly specific antibodies against the C-terminal end of amyloid-β42.
abstract: Alzheimer's disease (AD) is characterized by neurofibrillary tangles, consisting of hyperphosphorylated tau protein and senile plaques, which are consisting mainly of amyloid-β (Aβ). Attempts to generate a safe vaccine against Aβ rely on both B- and T-cell epitopes within the neurotoxic peptide Aβ1-42. This, however, poses a risk for an inflammatory and/or autoimmune response against Aβ-peptides in the brain. To overcome such risks we wanted to identify the shortest C-terminal Aβ-peptide that would induce antibodies selectively recognizing the C-terminal end of Aβ42. Immunization with this antigen should result in a non-inflammatory Th2 immune response and the T-cell response should be against a T-cell epitope covalently attached to the small Aβ-peptide. Antigen constructs were made by the ligand presenting assembly (LPA) technology, comprising dimeric presentation of short Aβ-peptides ending at amino acid 42 in connection with potent T-cell epitopes. Mice were immunized with antigen constructs using different adjuvants, and sera from mice were tested to characterize the generated immune response. Immunization with Keyhole limpet hemocyanin (KLH)-Aβ(37-42) resulted in generation of IgG1 antibodies specific for the Aβ42 C-terminal end, indicating a Th2-response. The T-cell mediated response was predominantly against T-cell epitopes in KLH. The antibodies stained senile plaques specifically in brain tissue from AD patients. Thus, KLH-Aβ(37-42) was able to induce a non-inflammatory and highly specific antibody response against Aβ42.
authors.affiliation: Loke Diagnostics ApS, Sindalsvej 17, DK-8240 Risskov, Denmark. trine@loke.dk
authors.forename: Trine Veje
authors.initials: TV
authors.lastname: Axelsen
authors.forename: Arne
authors.initials: A
authors.lastname: Holm
authors.forename: Gunna
authors.initials: G
authors.lastname: Christiansen
authors.forename: Svend
authors.initials: S
authors.lastname: Birkelund
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D000939:Epitopes / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood*; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D016229:Amyloid beta-Peptides; D000939:Epitopes; D007074:Immunoglobulin G; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)